Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

Int J Mol Sci. 2020 Dec 8;21(24):9338. doi: 10.3390/ijms21249338.

Abstract

Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to the abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes, which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of KP alterations observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota in the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

Keywords: Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; biomarkers; kynurenines; multiple sclerosis; neurodegenerative disease; personalized medicine; tryptophan.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Brain / metabolism
  • Gastrointestinal Microbiome
  • Humans
  • Kynurenine / metabolism*
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / microbiology
  • Neurodegenerative Diseases / pathology
  • Tryptophan / metabolism*

Substances

  • Biomarkers
  • Kynurenine
  • Tryptophan